Year: 2021
Type: article
Abstract: Accumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that transports intracellular cholesterol. These results suggest that the endocrine function of the vascular endothelium maintains glucose homeostasis. Of potential translational significance, the delivery of BMPER recombinant protein or its overexpression alleviates insulin resistance and hyperglycemia in high-fat diet-fed mice and Lepr db/db ( db/db) diabetic mice. We conclude that BMPER exhibits therapeutic potential for the treatment of diabetes.
Source: Nature Communications
Institution: Baylor College of Medicine
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Awards: Metabolic crosstalk through vascular endothelium-secreted factors, Signaling in Endothelial Growth and Angiogenesis, G2716752298, Regulation of Type 1 Inflammation in Diet-induced Obesity, G3331010138, LRP1 and endothelial function, G3455007010, G4059705364, G5664938880, Novel roles of Fe (2+), 2-oxoglutarate-dependent dioxygenases in cardiac function, G61165102, Monocyte Activation and the Role of CD11c in obesity-linked metabolic syndrome, G7422897710, G8185965056, G8804484951, G9000150754, G9000213352, G9000254706
OpenAlex ID: W3136223098